Hereditary pancreatitis is an autosomal dominant disease caused mostly by cationic trypsinogen (PRSS1) gene mutations.
In this study, a team of investigators from Europe and the United States determined the phenotype-genotype correlations of families in Europe.
They analyzed the data from the European Registry of Hereditary Pancreatitis and Pancreatic Cancer using multilevel proportional hazards modeling.
|The cumulative risk of pancreatic cancer was 44% at 70 years from symptom onset.|
|Clinical Gastroenterology and Hepatology|
Overall, the study identified 418 affected individuals from 112 families in 14 countries.
They found that 52% of families carried the R122H, 21% the N29I, and 4% the A16V mutation. A further 2 families had rare mutations, and that 19% had no PRSS1 mutation.
The investigators calculated that the median time to first symptoms was 10 years for R122H, 14 years for N29I, and 14.5 years for mutation negative patients.
They found that the cumulative risk at 50 years of age for exocrine failure was 37%, 48% for endocrine failure, and 18% for pancreatic resection for pain.
The team established that the time to resection was significantly reduced for females and subjects with the N29I mutation.
They found that the cumulative risk of pancreatic cancer was 44% at 70 years from symptom onset with a standardized incidence ratio of 67%.
Dr Nathan Howes and colleagues concluded, "Symptoms in hereditary pancreatitis start in younger patients."
"Endpoints take longer to be reached compared with other forms of chronic pancreatitis but the cumulative levels of exocrine and endocrine failure are much higher".
"There is an increasingly high risk of pancreatic cancer after the age of 50 years unrelated to the genotype".